P493: SINGLE CENTER EXPERIENCE OF VENETOCLAX (VEN) IN COMBINATION WITH FLAG-IDA IN PATIENTS (PTS) WITH NEWLY DIAGNOSED (ND) AND RELAPSED/REFRACTORY (R/R) ACUTE MYELOID LEUKEMIA (AML)
Authors: Y. Abaza, T. Khan, S. Dinner, O. Frankfurt, J. K. Altman
Journal: HemaSphere (2022)

Background: Despite the high complete remission (CR) rates achieved with intensive chemotherapy in AML, relapse rates remain high. This underscores the need for novel regimens capable of inducing deeper remissions via eradicating measurable residual disease (MRD). Recently, FLAG-IDA + VEN was shown to be an effective regimen in AML inducing high rates of MRD negative CR in both ND-AML and R/R AML allowing patients to be successfully bridged to allogenic stem cell transplantation (allo-SCT) (DiNardo 2021). Aims: Assess the clinical activity of FLAG-IDA + VEN in pts with high-risk AML Methods: We conducted a single-center retrospective study to assess the clinical activity of FLAG-IDA + VEN in a high-risk pt population. Standard cytogenetic (CN) testing was conducted and molecular data was obtained using a 40-gene next generation sequencing platform. Responses were based on the modified International Working Group criteria and included CR, CR with incomplete platelet recovery (CRp), morphologic leukemia-free state (MLFS), and partial remission (PR). Results: From March 2020 to January 2022, 17 pts with AML (10 ND and 7 R/R) were treated using FLAG-IDA + VEN (Table 1). Median age was 48 years (range, 21-68) with male predominance (76%). Among the 10 pts with ND-AML (5 de novo, 3 AML-MRC, 2 treated-secondary), 3 had extramedullary disease (EMD). The most common ELN cytogenetic risk groups were adverse (N=2), complex (N=4), and KMT2A-rearranged (N=2). Five pts (50%) harbored a RAS mutation. Median time to initiation of therapy was 5 days (range, 2-14). Five pts [KMT2A-r: 2; complex CN: 2; diploid: 1] achieved CR/CRp including 1 pt with EMD. Median time to count recovery (ANC ≥ 500 and platelets ≥ 50,000) was 21 days (range, 21- 42). Number of cycles of consolidation given to date were 1, 1, 1, 2, and 5 cycles, respectively, and none of these pts have received allo-SCT yet. MRD status was available for 3 pts of which 2 achieved MRD negativity using flow cytometry (<10-3) and one remained MRD positive (NPM1 PCR) after induction. With median follow-up of 4.7 months (range, 1.6-7.6), 4 pts remain alive in CR/CRp and 1 pt [complex CN, del 17p, TP53 mutant (VAF: 90%)] relapsed after 2 cycles of therapy with no response to salvage decitabine (DAC) plus VEN and died due to progressive disease (PD). Of the remaining 5 nonresponders, 2 had treated-secondary AML, 2 with adverse CN [inv (3), -(7)], and 2 pts had EMD. All 5 pts died due to PD including 3 pts who had no response to salvage therapy. Among the 7 pts with R/R AML, 6 were in salvage 1 and 1 pt received prior allo-SCT. Responses were observed in all patients: 4 CR, 1 CRp, 1 MLFS, and 1 PR. Median time to count recovery in R/R AML pts was 33 days (range, 24-78). Of the 5 pts who achieved CR/CRp, 4 were bridged to allo-SCT and 1 pt died in CR after 3 cycles of consolidation due to sepsis. Of the 4 SCT recipients, 2 pts relapsed 2 months post-SCT (1 died due to PD, 1 alive receiving salvage therapy) and 2 remain alive in CR for 4+ and 9+ months, respectively. The 2 pts who achieved MLFS and PR died due to PD and fungal pneumonia after 5 and 1.5 months of starting therapy, respectively. After median follow-up of 5.3 months (range, 0.7-13.2), median overall survival for the entire population was 6.2 months and the median duration of response for all pts who achieved CR/CRp was not reached. Image:Summary/Conclusion: FLAG-IDA plus VEN is a feasible and active regimen in AML. Longer follow-up and larger multicenter studies are needed to confirm the efficacy of this regimen.